During metabolic acidosis, the majority of renal H ion is excreted as NH4 ion; NH3 being provided by enhanced deamidation of glutamine to form glutamate followed by enhanced deamination of the formed glutamate. The remaining carbon skeleton provides a major fuel during acidosis for the kidney by its subsequent oxidation. The mechanisms increasing ammoniagenesis by kidneys during acidosis are as yet unknown; however, based on current thinking one can simplify the problem by determining whether deamidation drives deamination or vice versa. From previous experience, we favor a hypothesis that deamination drives deamidation and wish to prove this more conclusively by correlating augmented ammonia excretion during acidosis with tissue metabolism of glutamine and glutamate and by following N15 amide and amino NH3 formation in renal slices according to a plan outlined in the grant proposal. Believing that the glutamate dehydrogenase pathway is the rate limiting step regulating renal ammoniagenesis in response to acid-base changes, we wish to discover what factors regulate glutamate deamination. This includes investigating the competition for utilization and oxidation between various substrates (renal fuels such as lactate, palmitate, citrate and gamma-keto-glutarate) during acidosis, control and alkalotic states. These studies may lead to an understanding of whether changes in fuel utilization affect various metabolic and transport systems in the kidney. For instance, following acute or chronic acid challenge, spontaneous hypertensive rats produce less renal ammonia than control rats. This suggests to us altered renal metabolism in hypertensive rats compared to control rats and may even indicate a shift in metabolism from an aerobic to a more anaerobic one.